Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster Randomized Controlled Trial: Annals of Internal Medicine: Vol 167, No 9

Background: Inappropriate prescribing is a well-known clinical problem in nursing home residents, but few interventions have focused on reducing inappropriate medication use. Objective: To examine successful discontinuation of inappropriate medication use and to improve prescribing in nursing home residents. Design: Pragmatic cluster randomized controlled trial, with clustering by elder care physicians and their wards. (ClinicalTrials.gov: NCT01876095) Setting: 59 Dutch nursing home wards for long-term care. Patients: Residents with a life expectancy greater than 4 weeks who consented to treatment with medication. Intervention: Multidisciplinary Multistep Medication Review (3MR) consisting of an assessment of the patient perspective, medical history, critical appraisal of medications, a meeting between the treating elder care physician and the pharmacist, and implementation of medication changes. Measurements: Successful discontinuation of use of at least 1 inappropriate drug (that is, without relapse or severe withdrawal symptoms) and clinical outcomes (neuropsychiatric symptoms, cognitive function, and quality of life) after 4 months of follow-up. Results: Nineteen elder care physicians (33 wards) performed the 3MR, and 16 elder care physicians (26 wards) followed standard procedures. A total of 426 nursing home residents (233 in the intervention group and 193 in the control group) were followed for an average of 144 days (SD, 21). In an analysis of all participants, use of at least 1 inappropriate medication was successfully discontinued for 91 (39.1%) residents in the intervention group versus 57 (29.5%) in the control group (adjusted relative risk, 1.37 [95% CI, 1.02 to 1.75]). Clinical outcomes did not deteriorate between baseline and follow-up. Limitations: The 3MR was done only once. Some withdrawal symptoms or relapses may have been missed. Conclusion: The 3MR is effective in discontinuing inappropriate medication use in frail nursing home residents without a decline in their well-being. Primary Funding Source: Netherlands Organisation for Health Research and Development.

Can Primary Care Practices Help Address the Health Crisis Fueled by Prescription Opioids?

Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial: Annals of Internal Medicine: Vol 166, No 8

Background: Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS). Objective: To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS. Design: Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210) Setting: University hospital in the Netherlands. Patients: 50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment. Intervention: Participants were randomly assigned to daily subcutaneous anakinra, 100 mg (n = 25), or placebo (n = 25) for 4 weeks and were followed for an additional 20 weeks after treatment (n = 50). Measurements: The primary outcome was fatigue severity, measured by the Checklist Individual Strength subscale (CIS-fatigue) at 4 weeks. Secondary outcomes were level of impairment, physical and social functioning, psychological distress, and pain severity at 4 and 24 weeks. Results: At 4 weeks, 8% (2 of 25) of anakinra recipients and 20% (5 of 25) of placebo recipients reached a fatigue level within the range reported by healthy persons. There were no clinically important or statistically significant differences between groups in CIS-fatigue score at 4 weeks (mean difference, 1.5 points [95% CI, −4.1 to 7.2 points]) or the end of follow-up. No statistically significant between-group differences were seen for any secondary outcome at 4 weeks or the end of follow-up. One patient in the anakinra group discontinued treatment because of an adverse event. Patients in the anakinra group had more injection site reactions (68% [17 of 25] vs. 4% [1 of 25]). Limitation: Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms. Conclusion: Peripheral IL-1 inhibition using anakinra for 4 weeks does not result in a clinically significant reduction in fatigue severity in women with CFS and severe fatigue. Primary Funding Source: Interleukin Foundation and an independent donor who wishes to remain anonymous.

Rock Bottom

Maintenance of Weight Loss After Initiation of Nutrition Training: A Randomized Trial: Annals of Internal Medicine: Vol 166, No 7

Background: Weight regain after successful weight loss interventions is common. Objective: To establish the efficacy of a weight loss maintenance program compared with usual care in obese adults. Design: 2-group, parallel, randomized trial stratified by initial weight loss (<10 kg vs. ≥10 kg), conducted from 20 August 2012 to 18 December 2015. Outcome assessors were blinded to treatment assignment. (ClinicalTrials.gov: NCT01357551) Setting: 3 primary care clinics at the Veterans Affairs Medical Center in Durham and Raleigh, North Carolina. Patients: Obese outpatients (body mass index ≥30 kg/m2) who lost 4 kg or more of body weight during a 16-week, group-based weight loss program. Intervention: The maintenance intervention, delivered primarily by telephone, addressed satisfaction with outcomes, relapse-prevention planning, self-monitoring, and social support. Usual care involved no contact except for study measurements. Measurements: Primary outcome was mean weight regain at week 56. Secondary outcomes included self-reported caloric intake, walking, and moderate physical activity. Results: Of 504 patients in the initial program, 222 lost at least 4 kg of body weight and were randomly assigned to maintenance (n = 110) or usual care (n = 112). Retention was 85%. Most patients were middle-aged white men. Mean weight loss during initiation was 7.2 kg (SD, 3.1); mean weight at randomization was 103.6 kg (SD, 20.4). Estimated mean weight regain was statistically significantly lower in the intervention (0.75 kg) than the usual care (2.36 kg) group (estimated mean difference, 1.60 kg [95% CI, 0.07 to 3.13 kg]; P = 0.040). No statistically significant differences in secondary outcomes were seen at 56 weeks. No adverse events directly attributable to the intervention were observed. Limitations: Results may not generalize to other settings or populations. Dietary intake and physical activity were self-reported. Duration was limited to 56 weeks. Conclusion: An intervention focused on maintenance-specific strategies and delivered in a resource-conserving way modestly slowed the rate of weight regain in obese adults. Primary Funding Source: Veterans Affairs Health Services Research and Development Service.

Forbidden Topics

Exercise as Medicine

The Scientific Basis of Guideline Recommendations on Sugar Intake: A Systematic Review: Annals of Internal Medicine: Vol 166, No 4

Background: The relationship between sugar and health is affected by energy balance, macronutrient substitutions, and diet and lifestyle patterns. Several authoritative organizations have issued public health guidelines addressing dietary sugars. Purpose: To systematically review guidelines on sugar intake and assess consistency of recommendations, methodological quality of guidelines, and the quality of evidence supporting each recommendation. Data Sources: MEDLINE, EMBASE, and Web of Science (1995 to September 2016); guideline registries; and gray literature (bibliographies, Google, and experts). Study Selection: Guidelines addressing sugar intake that reported their methods of development and were published in English between 1995 and 2016. Data Extraction: Three reviewers independently assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II), instrument. To assess evidence quality, articles supporting recommendations were independently reviewed and their quality was determined by using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods. Data Synthesis: The search identified 9 guidelines that offered 12 recommendations. Each of the reviewed guidelines indicated a suggested decrease in the consumption of foods containing nonintrinsic sugars. The guidelines scored poorly on AGREE II criteria, specifically in rigor of development, applicability, and editorial independence. Seven recommendations provided nonquantitative guidance; 5 recommended less than 25% to less than 5% of total calories from nonintrinsic sugars. The recommendations were based on various health concerns, including nutrient displacement, dental caries, and weight gain. Quality of evidence supporting recommendations was low to very low. Limitation: The authors conducted the study independent of the funding source, which is primarily supported by the food and agriculture industry. Conclusion: Guidelines on dietary sugar do not meet criteria for trustworthy recommendations and are based on low-quality evidence. Public health officials (when promulgating these recommendations) and their public audience (when considering dietary behavior) should be aware of these limitations. Primary Funding Source: Technical Committee on Dietary Carbohydrates of the North American branch of the International Life Sciences Institute. (PROSPERO: CRD42015029182)

Mindfulness-Based Stress Reduction for Treating Low Back Pain: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 166, No 11

Background: Mindfulness-based stress reduction (MBSR) is frequently used to treat pain-related conditions, but its effects on low back pain are uncertain. Purpose: To assess the efficacy and safety of MBSR in patients with low back pain. Data Sources: Searches of MEDLINE/PubMed, Scopus, the Cochrane Library, and PsycINFO to 15 June 2016. Study Selection: Randomized controlled trials (RCTs) that compared MBSR with usual care or an active comparator and assessed pain intensity or pain-related disability as a primary outcome in patients with low back pain. Data Extraction: Two reviewers independently extracted data on study characteristics, patients, interventions, outcome measures, and results at short- and long-term follow-up. Risk of bias was assessed using the Cochrane risk-of-bias tool. Data Synthesis: Seven RCTs involving 864 patients with low back pain were eligible for review. Compared with usual care, MBSR was associated with short-term improvements in pain intensity (4 RCTs; mean difference [MD], −0.96 point on a numerical rating scale [95% CI, −1.64 to −0.34 point]; standardized mean difference [SMD], −0.48 point [CI, −0.82 to −0.14 point]) and physical functioning (2 RCTs; MD, 2.50 [CI, 0.90 to 4.10 point]; SMD, 0.25 [CI, 0.09 to 0.41 point]) that were not sustained in the long term. Between-group differences in disability, mental health, pain acceptance, and mindfulness were not significant at short- or long-term follow-up. Compared with an active comparator, MBSR was not associated with significant differences in short- or long-term outcomes. No serious adverse events were reported. Limitation: The number of eligible RCTs was limited; only 3 evaluated MBSR against an active comparator. Conclusion: Mindfulness-based stress reduction may be associated with short-term effects on pain intensity and physical functioning. Long-term RCTs that compare MBSR versus active treatments are needed in order to best understand the role of MBSR in the management of low back pain. Primary Funding Source: None.

Should We Screen for Vitamin D Deficiency?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 165, No 11

The U.S. Preventive Services Task Force (USPSTF) recently issued guidelines on screening for vitamin D deficiency. The guidelines were based on randomized trials of vitamin D deficiency screening and treatment, as well as on case–control studies nested within the Women's Health Initiative. The USPSTF concluded that current evidence is insufficient to assess the benefits and harms of screening for vitamin D deficiency in asymptomatic adults. Compared with placebo or no treatment, vitamin D was associated with decreased mortality; however, benefits were no longer seen after trials of institutionalized persons were excluded. Vitamin D treatment was associated with a possible decreased risk for at least 1 fall and the total number of falls per person but not for fractures. None of the studies examined the effects of vitamin D screening versus not screening on clinical outcomes. In this Grand Rounds, 2 prominent endocrinologists debate the issue of screening for vitamin D deficiency in a 55-year-old, asymptomatic, postmenopausal woman. They review the data on which the USPSTF recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of screening for vitamin D deficiency in primary care practice.